Exploring the Inclusion Complex of an Anticancer Drug with ß-Cyclodextrin for Reducing Cytotoxicity Toward the Normal Human Cell Line by an Experimental and Computational Approach.

The toxicity of any drug against normal cells is a health hazard for all humans. At present, health and disease researchers from all over the world are trying to synthesize designer drugs with diminished toxicity and side effects. The purpose of the present study is to enhance the bioavailability and biocompatibility of gemcitabine (GEM) by decreasing its toxicity and reducing deamination during drug delivery by incorporating it inside the hydrophobic cavity of ß-cyclodextrin (ß-CD) without affecting the drug ability of the parent compound (GEM). The newly synthesized inclusion complex (IC) was characterized by different physical and spectroscopic techniques, thereby confirming the successful incorporation of the GEM molecule into the nanocage of ß-CD. The molecular docking study revealed the orientation of the GEM molecule into the ß-CD cavity (-5.40 kcal/mol) to be stably posed for ligand binding. Photostability studies confirmed that the inclusion of GEM using ß-CD could lead to better stabilization of GEM (≥96%) for further optical and clinical applications. IC (GEM-ß-CD) and GEM exhibited effective antibacterial and antiproliferative activities without being metabolized in a dose-dependent manner. The CT-DNA analysis showed sufficiently strong IC (GEM-ß-CD) binding (Ka = 8.1575 × 1010), and this interaction suggests that IC (GEM-ß-CD) may possibly exert its biological effects by targeting nucleic acids in the host cell. The newly synthesized biologically active IC (GEM-ß-CD), a derivative of GEM, has pharmaceutical development potentiality.

ß-Cyclodextrin-Stabilized Biosynthesis Nanozyme for Dual Enzyme Mimicking and Fenton Reaction with a High Potential Anticancer Agent.

The myth of inactivity of inorganic materials in a biological system breaks down by the discovery of nanozymes. From this time, the nanozyme has attracted huge attention for its high durability, cost-effective production, and easy storage over the natural enzyme. Moreover, the multienzyme-mimicking activity of nanozymes can regulate the level of reactive oxygen species (ROS) in an intercellular system. ROS can be generated by peroxidase (POD), oxidase (OD), and Fenton-like catalytic reaction by a nanozyme which kills the cancer cells by oxidative stress; therefore, it is important in CDT (chemo dynamic therapy). Our current study designed to investigate the enzyme mimicking behavior and anticancer ability of cerium-based nanomaterials because the cerium-based materials offer a high redox ability while maintaining nontoxicity and high stability. Our group synthesized CeZrO4 nanoparticles by a green method using ß-cyclodextrin as a stabilizer and neem leaf extract as a reducing agent, exhibiting POD- and OD-like dual enzyme activities. The best enzyme catalytic activity is shown in pH = 4, indicating the high ROS generation in an acidic medium (tumor microenvironment) which is also supported by the Fenton-like behavior of CeZrO4 nanoparticles. Inspired by the high ROS generation in vitro method, we investigated the disruption of human kidney cells by this nanoparticle, successfully verified by the MTT assay. The harmful effect of ROS in a normal cell is also investigated by the in vitro MTT assay. The results suggested that the appreciable anticancer activity with minimal side effects by this synthesized nanomaterial.